The objective of the proposed research is to define the mechanism by which bacterial endotoxin mitigates the reactivity of transplanted immunocompetent murine cells against normal mouse tissues without abolishing their capacity to kill tumor cells. In the planned experiments, we seek to optimize endotoxin treatment so as to maximally reduce GVH mortality when H-2 incompatible spleen cells are given to immunosuppressed recipient mice; to study the kinetics of the phenomenon; to investigate other B cell activators for similar activity; and to test splenic plastic adherent and nonadherent populations for putative suppressor cells. We will test procedures for decreasing GVH reactivity of donor spleen cells by incubating them with endotoxin in vitro and compare the effect of endotoxin treatment in vivo and/or in vitro on the GVH reactivity of donor cells in various histoincompatible donor-recipient strain combinations. Using a sensitive bioassay system, we will study the reactivity of DBA/2 (H-2d) cells treated with endotoxin in vivo or in vitro against spontaneous leukemia-lymphoma in AKR (H-2k) mice. Cells exhibiting the highest antileukemic reactivity will then be used in combination with drugs and radiation for adoptive immunotherapy of AKR spontaneous leukemia-lymphoma. The planned study should contribute significant information regarding the immunological reaction against cancer and help elucidate successful approaches to the immunotherapy of malignancy.